The early detection of lung cancer is critical to improving the mortality rate associated with lung cancer. Studies from the Lung Cancer Study Group have shown that the 5-year survival of patients with very early stage non- small cell lung cancer (T1N0M0) is 80%, far better than the overall 10% 5- year survival for lung cancer. We have had an ongoing collaboration with Dean Cole at the Los Alamos National Laboratory to evaluate a new photoactive porphyrin compound for the detection of early lung neoplasms, and use a radiolabeled form of this compound for local ablation of abnormal bronchial epithelium (in project Z01 CN 00169-02 BPRB). This project is awaiting further development of the porphyrin compound. During Summer 1993, protocols for the early detection of lung cancer among individuals at high risk will be submitted for approval. We propose to target lung cancer and head and neck cancer survivors with serial monitoring of sputum and bronchoscopically obtained specimens to assay for biomarker expression. The study design will incorporate comparison of ~ndings in different specimens such as bronchial washings, bronchial biopsies at multiple sites and expectorated sputum. Particularly important would be whether or not the markers are differentially expressed in the unaffected portions of the lung or only detectable in certain types of specimens. A subset of subjects will be enrolled in an intervention trial. Specimens will be obtained at on-study, after the period of intervention and roughly 3 months after the intervention is stopped. The ~rst intervention trial anticipated will use 4-HPR if available, or low dose 13-cis-retinoic acid. Future intervention agents for this subject population might include Vitamin E or the radiolabeled photoactive porphyrin compound for a 3-6 month period. Pharmacokinetic studies will also be incorporated to evaluate the effect of dose on marker modulation as well as to evaluate alternative forms of administration such as aerosolization of the agents. The success of early detection of cancer is dependent upon the ability to intervene successfully at that early stage to prevent the morbidity and mortality associated with cancer and standard therapy. Published reports have suggested that genomic p53 mutations may be present in individuals with an inherited susceptibility to several types of cancer, including but not limited to Li-Fraumeni syndrome. A similar study using genomic DNA from whole blood collected during a case-control study of lung cancer is planned to evaluate markers of susceptibility to lung cancer.